Characterization of a cytosolic heat-shock protein caveolin chaperone complex - Involvement in cholesterol trafficking (Retracted Article)
Characterization of a cytosolic heat-shock protein caveolin chaperone complex - Involvement in cholesterol trafficking (Retracted Article)
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DOI：
10.1074/jbc.273.11.6525
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发表时间：
1998-03-13
影响因子：
4.8
通讯作者：
Smart, EJ
中科院分区：
文献类型：
--
作者：
Uittenbogaard, A;Ying, YS;Smart, EJ
小窝蛋白是一种分子量为22-kDa的蛋白质，在调节小窝的胆固醇浓度中起着关键作用。尽管小窝蛋白被认为是一种膜蛋白，但一些报道表明这种特殊的蛋白质可以独立于膜囊泡进行运输。我们现在提出的证据表明，小窝蛋白的胞质池是由小窝蛋白组成的热休克蛋白-亲免蛋白伴侣复合物的一部分，热休克蛋白56、亲环素40、亲环素A和胆固醇。用1 μ m环孢菌素A或100 nM雷帕霉素处理MH 3 T3细胞，破坏了假定的转运复合物，并阻止了快速转运。淋巴细胞系L1210-JF不表达小窝蛋白，不形成亲免蛋白-小窝蛋白复合物，并且不将新合成的胆固醇转运到小窝，将小窝蛋白cDNA转染L1210-JF细胞，可使其组装成与NIH 3 T3细胞相同的转运复合物。（10-20分钟）并特异性地运输至小窝，这些数据有力地表明，一个洞穴-伴侣复合物是新合成的胆固醇从内质网通过细胞质转运到小窝的机制。
Caveolin is a 22-kDa protein that appears to play a critical role in regulating the cholesterol concentration of caveolae, Even though caveolin is thought to be a membrane protein, several reports suggest that this peculiar protein can traffic independently of membrane vesicles, We now present evidence that a cytosolic pool of caveolin is part of a heat-shock protein-immunophilin chaperone complex consisting of caveolin, heat-shock protein 56, cyclophilin 40, cyclophilin A, and cholesterol. Treatment of MH 3T3 cells with 1 mu m cyclosporin A or 100 nM rapamycin disrupted the putative transport complex and prevented rapid (10-20 min) transport of cholesterol to caveolae, The lymphoid cell line, L1210-JF, does not express caveolin, does not form an immunophilin-caveolin complex, and does not transport newly synthesized cholesterol to caveolae, Transfection of caveolin cDNA into L1210-JF cells allowed the assembly of a transport complex identical to that found in NIH 3T3 cells, In addition, newly synthesized cholesterol in transfected cells was rapidly (10-20 min) and specifically transported to caveolae, These data strongly suggest that a caveolin-chaperone complex is a mechanism by which newly synthesized cholesterol is transported from the endoplasmic reticulum through the cytoplasm to caveolae.